Epigenetic Regulation of Immune Responses in Chickens: Mechanisms, Host–Pathogen Interactions, and Emerging Genomic Technologies

Epigenetic regulation has emerged as a fundamental mechanism governing immune function in poultry by integrating genetic, environmental, nutritional, and microbial signals without altering the DNA sequence. Recent advances in epigenomics have revealed that DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs are associated with regulation of immune and inflammatory responses, inflammatory signaling, immune-cell differentiation, and host–pathogen interactions. Poultry-specific studies, predominantly conducted in chickens, have identified infection- and challenge-associated epigenetic changes in models including avian influenza, Marek’s disease, and bacterial inflammatory stimulation, with the strongest current evidence relating to innate and inflammatory immune regulation. Environmental factors such as nutrition, gut microbiota, heat stress, and developmental conditions further shape immune competence through epigenetic programming, while emerging evidence suggests that some epigenetic modifications may contribute to transgenerational disease resistance. Emerging evidence suggests that some epigenetic signatures may persist across generations; however, robust evidence for stable transgenerational inheritance of immune-related epigenetic traits in poultry remains limited. Advances in whole-genome bisulfite sequencing, ATAC-seq, ChIP-seq, and single-cell multi-omics are improving characterization of the avian epigenome, whereas CRISPR-based epigenome editing, artificial intelligence-assisted prediction, epigenetic selection, and epigenome-informed vaccine optimization remain prospective applications requiring substantial functional and field validation. This review synthesizes current knowledge of epigenetic mechanisms regulating poultry immunity, evaluates their roles in host–pathogen interactions and environmental adaptation, and highlights emerging genomic technologies that may facilitate translation of immunoepigenetic discoveries into practical strategies for improving poultry health, disease resilience, and sustainable production.