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Oreochromis mossambicus is a euryhaline species that can endure a wide range of salinities and has the potential to serve as a valuable model animal for environmental science. In order to detect the histomorphological changes, antioxidant enzymes, and proteomic responses of O. mossambicus to different osmotic stresses, O. mossambicus was subjected to salinity stress (25 g\/L, S_S), alkalinity stress (4 g\/L, A_S), saline\u2013alkalinity stress (salinity: 25 g\/L, alkalinity: 4 g\/L, SA_S), and freshwater (the control group; C_S). The histomorphological and antioxidant enzyme results indicated that salinity, alkalinity, and saline\u2013alkalinity stresses have different degrees of damage and effects on the gills and liver of O. mossambicus. Compared with the control, 83, 187, and 177 differentially expressed proteins (DEPs) were identified in the salinity, alkalinity, and saline\u2013alkalinity stresses, respectively. The obtained DEPs can be summarized into four categories: ion transport channels or proteins, energy synthesis and metabolism, immunity, and apoptosis. The KEGG enrichment results indicated that DNA replication and repair were significantly enriched in the salinity stress group. Lysosomes and oxidative phosphorylation were considerably enriched in the alkalinity stress group. Comparatively, the three most important enriched pathways in the saline\u2013alkalinity stress group were Parkinson\u2019s disease, Alzheimer\u2019s disease, and Huntington\u2019s disease. The findings of this investigation yield robust empirical evidence elucidating osmoregulatory mechanisms and adaptive biological responses in euryhaline teleost, thereby establishing a scientific foundation for the cultivation and genomic exploration of high-salinity-tolerant teleost species. This advancement facilitates the sustainable exploitation of saline\u2013alkaline aquatic ecosystems while contributing to the optimization of piscicultural practices in hypersaline environments.<\/jats:p>","DOI":"10.3390\/ijms26062791","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T05:03:59Z","timestamp":1742447039000},"page":"2791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A TMT-Based Proteomic Analysis of Osmoregulation in the Gills of Oreochromis mossambicus Exposed to Three Osmotic Stresses"],"prefix":"10.3390","volume":"26","author":[{"given":"Huanhuan","family":"Su","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical & Subtropical Fishery Resource Application & Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Science, No. 1, Xingyu Road, Liwan District, Guangzhou 510380, China"},{"name":"Heyuan Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Heyuan 517000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical & Subtropical Fishery Resource Application & Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Science, No. 1, Xingyu Road, Liwan District, Guangzhou 510380, China"},{"name":"Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical & Subtropical Fishery Resource Application & Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Science, No. 1, Xingyu Road, Liwan District, Guangzhou 510380, China"},{"name":"Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4261-9894","authenticated-orcid":false,"given":"Zaixuan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical & Subtropical Fishery Resource Application & Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Science, No. 1, Xingyu Road, Liwan District, Guangzhou 510380, China"},{"name":"Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Tian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical & Subtropical Fishery Resource Application & Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Science, No. 1, Xingyu Road, Liwan District, Guangzhou 510380, China"},{"name":"Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical & Subtropical Fishery Resource Application & Cultivation, Ministry of Agriculture and Rural Affairs, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Science, No. 1, Xingyu Road, Liwan District, Guangzhou 510380, China"},{"name":"Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/jez.2350","article-title":"The cellular stress response in fish exposed to salinity fluctuations","volume":"333","author":"Evans","year":"2020","journal-title":"J. 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