Understanding migratory behavior, mortality, and physiology is essential for conservation of many species, particularly anadromous fish. In this study, freshwater and marine migrations of the endangered salmonid North Sea houting (Coregonus oxyrinchus (Linnaeus, 1758)) were investigated using telemetry. Furthermore, physiological samples were collected from North Sea houting and from resident and anadromous populations of the closely related European whitefish (Coregonus lavaretus (Linnaeus, 1758)) to compare hypo-osmotic tolerances. On average, North Sea houting spent 193 days at sea where the mortality was 36%. Most fish returned from sea in the autumn, and river entry correlated inversely with river temperature and positively with discharge. Fish spent an average of 49 days in the estuarine area. Artificial lakes negatively affected migration speeds. Migration speeds did not differ consistently between individuals (i.e., not a repeatable trait) but correlated positively with water temperature. Fish arrived at spawning areas in November. In the post-spawning state, Na+/K+-ATPase activities were elevated in North Sea houting and anadromous whitefish compared with resident whitefish, while osmolality was elevated only in North Sea houting. Our study provides important information for conservation planning related to the Habitat Directive of the European Union that lists the North Sea houting as critically endangered.