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This may deteriorate fish health and productivity, and threaten the sustainability of aquaculture. Hence, the current study was carried out to investigate the interactions between hypoxia and increased salinity, as well as their impact on growth parameters, digestive enzymes, serum biochemistry, antioxidative response, and histopathology in Nile tilapia (\n                    <jats:italic>Oreochromis niloticus<\/jats:italic>\n                    ). A total of 270 juvenile fish were impartially allocated into 18 aquariums (six treatments with three replicates) in a 2\u2009\u00d7\u20093 factorial design, which included two oxygen levels (normoxia\u2009=\u20095.5\u20136\u00a0mg\/L DO\n                    <jats:sub>2<\/jats:sub>\n                    and hypoxia\u2009=\u20091\u20131.5\u00a0mg\/L DO\n                    <jats:sub>2<\/jats:sub>\n                    ) and three salinity conditions (0, 7, and 14\u00a0g\/L) over 56\u00a0days feeding on a commercial diet (32% protein). Salinity and hypoxia significantly reduced growth and feed utilization. The most declared weight gain and feed conversion ratios were obtained under normoxic and freshwater conditions, although the survival rate was not considerably altered. Hypoxia increased RBCs, hemoglobin, and hematocrit, while elevated salinity significantly reduced them. Hypoxia and elevated salinity impaired digestive enzymes (protease, lipase, \u03b1-amylase), increased plasma cortisol, glucose, and liver enzyme levels (aspartate aminotransferase and alanine aminotransferase), lipid profile levels (total cholesterol and triglycerides), while decreasing plasma total protein. The immunity response (lysozyme activity, respiratory burst, phagocytosis, and IgM) was markedly reduced under hypoxia and hypersalinity, while they were markedly enhanced under normoxia and freshwater conditions. Fish reared under hypoxia and higher salinity exhibited structural damage in gills, intestine, and liver tissues. Our findings show that environmental stressors (hypoxia and excessive salinity) harm Nile tilapia growth and well-being, emphasizing the need to improve aquaculture settings in response to climate change.\n                  <\/jats:p>","DOI":"10.1007\/s10695-025-01608-6","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T10:02:48Z","timestamp":1765188168000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Interactive impact of salinity and oxygen level on the growth performance, digestive enzymes, serum biochemistry, antioxidative, immunity, and histological status of Nile tilapia (Oreochromis niloticus)"],"prefix":"10.1007","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3754-5966","authenticated-orcid":false,"given":"Mohamed N.","family":"Monier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherien H. 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