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Tilapiine fishes of the genus Oreochromis vary in their euryhaline capabilities, therefore inhabiting aquatic environments of different salinities across the African continent. We analyzed the differential gene expression in the gills before and after 6 weeks salinity challenge between the highly tolerant Mozambique tilapia (Oreochromis mossambicus) and the less tolerant Nile tilapia (O. niloticus). The pathways triggered by salinity in both tilapia species reveal immune and cell stress responses as well as turnover of ionocytes. Nevertheless, the actual differential expressed genes vary between these two species, pointing at differential transcriptomic architecture, which likely contribute to the species osmoregulation capabilities in elevated salinities. [Display omitted] • Different transcriptomic architecture after salinity challenge between tolerant and sensitive tilapiine species. • RNAseq technique reveals expression of pseudogenomes in close species under osmotic stress. • Immune strategy varies in gills of two tilapia species after salinity exposure. • Same physiological pathways triggered by different genes between two species for coping with cell stress induced by salinity. [ABSTRACT FROM AUTHOR]