Livestock Immunogenomics Based on Omics Integration: from Infection and Stress to Xenotransplantation

Livestock production systems are increasingly constrained by infectious diseases and environmental stress, which compromise productivity, animal welfare, and sustainability under heterogeneous field conditions. Immune-related traits that govern disease susceptibility, recovery, and performance loss are inherently polygenic, context-dependent, and expressed through coordinated responses across multiple tissues and molecular layers. Consequently, single-omics approaches often fail to generalize across breeds, environments, and management systems, limiting their translational value in improving livestock health. Livestock immunogenomics has emerged as a framework for addressing this complexity by integrating genetic variation with the regulatory, cellular, and metabolic programs that shape immune competence and resilience to disease. In recent years, substantial progress in functional genome annotation, genotype–tissue regulatory atlases, and single-cell reference datasets has strengthened the foundation for systems-level analyses of the major livestock species. However, effective translation requires multiomics integration strategies that are aligned with field-relevant phenotypes and designed to remain interpretable under distribution shifts driven by co-infections, environmental stressors, and management variability. In this review, we synthesized computational and experimental strategies for omics integration in livestock immunogenomics and examined their applications in three major domains: infectious diseases, environmental stress, and xenotransplantation. We highlight design principles that consistently improve interpretability and transportability, including longitudinal and phase-aware sampling, compartment-resolved analysis across tissues, integration of regulatory layers, and explicit reduction of complex multiomics outputs into deployable signatures. Case studies on cattle, swine, and poultry have illustrated how integrative frameworks distinguish protective immune programs from inflammation-associated damage, link molecular modules to resilience-related phenotypes, and support their incorporation into precision health management and breeding strategies. Beyond production systems, we discuss xenotransplantation as an extreme but informative translational setting in which livestock immunogenomics reveals how immune outcomes emerge from coordinated regulatory and metabolic programs rather than from individual antigenic mismatches. Collectively, this review emphasizes that the future impact of livestock immunogenomics does not increase data dimensionality but treats omics integration as a translational pipeline that connects systems-level immune biology to practical interventions for animal health, welfare, and sustainable production.