Livestock immunogenomics based on omics integration: from infection and stress to xenotransplantation.

Livestock production systems are increasingly constrained by infectious diseases and environmental stress. These factors compromise productivity, animal welfare, and sustainability under heterogeneous field conditions. Immune-related traits governing disease susceptibility, recovery, and performance loss are polygenic and influenced by diverse conditions. They arise from coordinated responses across multiple tissues and molecular layers. As a result, 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 linking genetic variation with regulatory, cellular, and metabolic programs that shape immune competence and resilience across diverse biological and production conditions. 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 in major livestock species. However, effective translation requires integrative strategies aligned with field-relevant phenotypes and capable of remaining interpretable under varying production and biological conditions. In this review, we synthesized computational and experimental strategies for omics integration in livestock immunogenomics and examined their applications across three major domains: infectious diseases, environmental stress, and xenotransplantation. We highlight design principles that improve interpretability and transportability, including longitudinal sampling, phase-aware designs across stages of the response, compartment-resolved analysis across tissues, integration of regulatory layers, and explicit reduction of complex outputs into deployable signatures. Case studies in cattle, swine, and poultry illustrate how integrative frameworks distinguish protective immune programs from inflammation-associated damage, link molecular modules to resilience-related phenotypes, and support their application in precision health management and breeding strategies. Beyond production systems, we discuss xenotransplantation as an extreme but informative translational setting. In this context, 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 lies not in increasing data dimensionality, but treating omics integration as a translational pipeline that connects systems-level immune biology to practical interventions for animal health, welfare, and sustainable production.