International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 22-31 http://animalscipublisher.com/index.php/ijmvr 27 5.4 Effects of domestication on disease resistance and pathogen susceptibility Domestication has generated intense selection on regulatory genes and regions, with reduced nucleotide diversity but maintenance of functionally important CNVs and immune gene variants in dogs (Wang et al., 2018). Domesticated dogs have hypermethylation of immune loci and impaired immune function relative to their wild progenitors, like other domestic species (Fu et al., 2025). Selection within domestication has targeted genes associated with stress response and behavior, which can, indirectly, affect immune function and disease susceptibility. Introgressive adaptation from the domestic to the wild lineage of canids has the potential to introduce advantageous immune alleles that affect disease resistance in wild canid populations (Sarabia et al., 2025). 6 Integration of Multi-Omics in Canine Pathogen Research 6.1 Insights from genomics and transcriptomics into pathogen infection mechanisms Genomic and transcriptomic approaches have greatly advanced understanding of mechanisms of pathogen infection in dogs. Whole-transcriptome analysis of Leishmania infantum-infected dogs has identified thousands of differential expressed genes that identify major immune pathways, cytokine responses, and regulatory modules that participate in the disease progression and immune exhaustion (Sanz et al., 2022). Transcriptomics is also used to annotate changes in host and pathogen gene expression during infection in order to determine virulence factors and immune evasion mechanisms (Elrashedy et al., 2025). Dual RNA-Seq and similar technologies allow for profiling of both host and pathogen simultaneously, providing a dynamic view of interaction between the two. 6.2 Applications of proteomics and metabolomics in studying host immune responses Proteomics and metabolomics must map host-pathogen interactions at protein and metabolic levels. Proteomic analysis of Toxocara canis- and Babesia canis-infected dogs identified the differentially expressed proteins participating in immune regulation, signal transduction, and metabolism, with specific interest in interference with intestinal permeability and immune suppression (Wang et al., 2024). Metabolomics has also revealed global alterations in lipid, energy, and amino acid metabolism following infection, important in disease pathology as well as for biomarkers of diagnosis and treatment (Kuleš et al., 2025). Co-enriched pathways, i.e., bile secretion, are identified by integration of proteomic and metabolomic data sets, which are critical for host-pathogen interaction (Wang et al., 2024). 6.3 Advances in single-cell and spatial omics for host-pathogen interaction research Single-cell genomics and spatial multi-omics capability can now empower scientists to anatomize host-pathogen interactions at unprecedented levels of granularity. These capabilities reveal biochemical heterogeneity in immune function and pathogen function and allow scientists to profile rare cell populations and spatially resolved molecular dynamics on infection (Gioacchino et al., 2024). Single-cell RNA sequencing has also been utilized to map transcriptional states in infected tissue and demultiplex immune cell exhaustion, persistence of the pathogen, and tissue-specific immune responses. 6.4 Construction of integrated multi-omics and systems biology models The integration of genomics, transcriptomics, proteomics, and metabolomics with advanced bioinformatics and systems biology enables one to create integrated models of host-pathogen interactions. Such models enable one to determine regulatory networks, disease modules, and biomarkers and create targeted diagnostics and therapeutics (Beltran et al., 2017; Khan et al., 2019). These public databases and computing resources, such as iDog, can now be employed for the integration of dog and comparative pathogen data, visualization, and hypothesis generation (Tang et al., 2018). 7 Research Challenges and Limitations 7.1 Incomplete genomic data and limited regional representation of samples Current genomic holdings of domestic dog-related zoonotic pathogens are geographically biased and incomplete. Since most downloadable genome information is contributed by domestic dogs from developed nations, wild canid species such as wolves, coyotes, and jackals have limited or patchy data. This disparity does not allow for
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