Multi-organ pathological injury and transcriptomic immunometabolic reprogramming induced by Photobacterium damselae infection

Bacterial enteritis caused by Photobacterium damselae poses a severe threat to marine aquaculture, particularly for golden pompano (Trachinotus ovatus). Although traditionally viewed as a localized gastrointestinal disorder, the systemic molecular mechanisms underlying host mortality and immune dysfunction remain poorly understood. We integrated histopathological evaluation, multi-organ transcriptomics, weighted gene co-expression network analysis (WGCNA), and protein–protein interaction network analysis to characterize host responses across 5 critical tissues: gill, intestine, liver, spleen, and kidney. Histological examination revealed severe multi-organ pathological alterations, including mucosal barrier disruption, hepatic and renal tissue damage, and splenic immune activation, indicating that P. damselae infection induces systemic pathological responses rather than a purely localized intestinal lesion. Transcriptomic and WGCNA analyses identified a coordinated immunometabolic regulatory axis involving five core hub genes, creb1, fos, myc, igf1, and pparg, which were associated with inflammatory signaling, cellular stress responses, and energy reallocation. Notably, the major histocompatibility complex class I (MHC-I) alpha-chain gene was consistently down-regulated across all examined tissues, whereas tap1 and b2m remained relatively stable. This selective disruption of the MHC-I antigen-presentation axis suggests a potential impairment of cellular immune recognition and may contribute to systemic immune dysfunction during infection. Collectively, these findings redefine P. damselae-associated enteritis as a complex multi-organ immunometabolic disorder. The identification of disrupted antigen presentation and central immunometabolic hubs provides a theoretical foundation and potential molecular targets for developing multi-target immunomodulatory strategies in marine aquaculture.