Added PubMed Id Acclimations of Oreochromis mossambicus to elevated salinity were conducted with multiple rates of salinity increase and duration of exposure to determine the rate-independent maximum salinity limit and the incipient lethal salinity. A data-independent acquisition (DIA) assay library was created for quantitative analysis of over 3000 gill proteins simultaneously in treatments representative of important key zones in the salinity level/duration landscape. From these DIA data, protein networks that represent complex molecular phenotypes associated with salinity acclimation were generated. Acclimations of Oreochromis mossambicus to elevated salinity were conducted with multiple rates of salinity increase and duration of exposure to determine the rate-independent maximum salinity limit and the incipient lethal salinity. A data-independent acquisition (DIA) assay library was created for quantitative analysis of over 3000 gill proteins simultaneously in treatments representative of important key zones in the salinity level/duration landscape. From these DIA data, protein networks that represent complex molecular phenotypes associated with salinity acclimation were generated. Protein fold change (FC) and organismal level performance indicators of salinity tolerance were then correlated. Gill protein networks impacted at extreme salinity levels both above and below the incipient lethal limit include increased energy metabolism, especially upregulation of electron transport chain complex proteins, and significant downregulation of a previously uncharacterized protein which bears strong amino acid sequence similarity to fucolectin. Proteins networks strongly impacted by crossing into the zone of resistance include cell adhesion and extracellular matrix regulation.