IntroductionThe pathogenesis ofVibrio mimicusinfection in yellow catfish (Pelteobagrus fulvidraco) remains poorly understood, particularly regarding the impact of infection with the pathogen on primary target organs such as the skin and muscle.MethodsIn this study, we aim to analyze the pathological intricacies of the skin and muscle of yellow catfish after being infected withV. mimicususing a 1/10 LC50seven-day post-infection model. Furthermore, we have utilized integrated bioinformatics to comprehensively elucidate the regulatory mechanisms and identify the key regulatory genes implicated in this phenomenon.ResultsOur histopathological examination revealed significant pathological changes in the skin and muscle, characterized by necrosis and inflammation. Moreover, tissue remodeling occurred, with perimysium degeneration and lesion invasion into the muscle along the endomysium, accompanied by a transformation of type I collagen into a mixture of type I and type III collagens in the perimysium and muscle bundles. Our eukaryotic transcriptomic and 4D label-free analyses demonstrated a predominantly immune pathway response in both the skin and muscle, with downregulation observed in several cell signaling pathways that focused on focal adhesion-dominated cell signaling pathways. The upregulated genes includedinterleukins(IL)-1 and -6,chemokines, andmatrix metallopeptidases(mmp)-9 and -13, while several genes were significantly downregulated, includingcol1aand col1a1a. Further analysis revealed that these pathways were differentially regulated, withmmp-9 andmmp-13 acting as the potential core regulators of cytokine and tissue remodeling pathways. Upregulation ofNF-κB1andFOSL-1induced byIL-17CandNox 1/2-based NADPH oxidase may have held matrix metallopeptidase and cytokine-related genes. Also, we confirmed these relevant regulatory pathways by qPCR and ELISA in expanded samples.DiscussionOur findings unequivocally illustrate the occurrence of a cytokine storm and tissue remodeling, mediated by interleukins, chemokines, and MMPs, in the surface of yellow catfish infected withV. mimicus. Additionally, we unveil the potential bidirectional regulatory role of MMP-9 and MMP-13. These results provide novel perspectives on the intricate immune response toV. mimicusinfection in yellow catfish and highlight potential targets for developing therapies.