Gibelion catla is an economically important fish species in Asian fish industry due to its suitability in polyculture system and high market value. Despite a valued market fish in Pakistan and serious threats of bacterial infections this fish is facing, studies concerning health status and disease resistance of G. catla are rare. Therefore, this study used label‐free quantification liquid chromatography‐mass spectrometry (LFQ—LC‐MS/MS) and identified infection‐biased expression of the protein in the skin mucus of G. catla after Aeromonas hydrophila infection. In total, 1545 proteins in the skin mucus of nontreated fish and 1400 proteins in the treated fish were identified, of which 1335 proteins overlapped between the two groups, 137 differentially expressed proteins (DEPs) were found, where 71 proteins were downregulated and 66 proteins were upregulated. Functionally, the 137 DEPs were immune‐related, bactericidal, and cytoskeleton proteins. The most significant and upregulated protein in the skin mucus of treated fish were ribosomal proteins (40S ribosomal protein S19 (20‐fold change (FC)), 60S ribosomal L7a (20‐FC), 60S ribosomal L12 isoform X1 (21‐FC), and 60S acidic ribosomal P0), beta‐actin (24‐FC), immunoglobulin mu heavy chain (20‐FC), glucose‐regulated protein 78 (GRP78; 20‐FC), epithelial cell adhesion molecule‐like protein (20‐FC), putative complement c 3.3 (20‐FC), 14 kDa apolipo (19‐FC), hemoglobin subunit beta‐like protein (19.3‐FC), annexin A1‐like protein (19‐FC), proliferating cell nuclear antigen (18‐FC), G‐type lysozyme (18‐FC), and keratins such as type I cytoskeletal 47 kDa‐like isoform X1 (23‐FC), and type II cytoskeletal 8 (23‐FC). In short, our study highlighted the proteins in the skin mucus of fish involved against bacterial infection, which could be possible biomarkers for further functional‐based studies. Particularly, the study elaborates the mucosal immune response of G. catla against A. hydrophila infection, which may help in the strategies of prevention and control of bacterial diseases in this fish.
