Beyond the Transcriptome: The m 6 A Epitranscriptome in Bovine Mastitis

Bovine mastitis is a heterogeneous inflammatory disease that compromises milk production, animal welfare and dairy sustainability. Despite extensive transcriptomic and epigenomic research, a PubMed search completed in September 2026 identified only 12 primary studies addressing epitranscriptomic regulation in bovine mastitis, representing approximately 0.1% of indexed publications. This review critically evaluates N 6 ‐methyladenosine (m 6 A), the most extensively studied RNA modification in bovine mastitis, its regulatory machinery and effects on mammary immunity, while identifying m 5 C and A‐to‐I editing as priorities for mechanistic investigation. Current evidence identifies transcript‐specific RNA stability as the best‐supported mechanism and provides a foundation for investigating m 6 A‐dependent translation. Functional studies of ALKBH5– LOC4191 , YTHDF2– IER3 , YTHDF2‐associated CCL20 and CCL5 regulation, m 6 A‐regulated LncRNA7825 and FTO– FN1 demonstrate that m 6 A reshapes inflammatory signalling, mitochondrial stress, epithelial‐barrier integrity, cell survival and bacterial control. Synthesizing these findings, we propose a context‐dependent RNA‐fate checkpoint model in which biological effects depend on the modified transcript, effector protein, pathogen, cellular context and infection phase. The FTO– FN1 axis shows that bacterial control and tissue protection can diverge, establishing them as complementary outcomes. Future studies should test whether m 6 A provides an early post‐transcriptional response layer and whether pathogens manipulate it, using time‐resolved multi‐omics, nucleotide‐specific perturbation, primary cells, mammary organoids and longitudinal cattle samples. Parallel profiling of non‐m 6 A modifications should define interacting regulatory layers. These approaches should establish causal modification sites, resolve pathogen‐specific regulation, connect molecular mechanisms with disease trajectories, and support validated milk‐based biomarkers, mammary‐targeted interventions and prioritization of stable genetic variants for breeding mastitis‐resistant cattle.