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Based on lake sediment data, archaeological findings, and historical records, we describe rapid transformations, resilience and resistance in societies and ecosystems, and their interactions in the past in the North Water area related to changes in climate and historical events. Examples are the formation of the polynya itself and the early arrival of people, ca. 4500 years ago, and later major human immigrations (different societies, cultural encounters, or abandonment) from other regions in the Arctic. While the early immigrations had relatively modest and localised effect on the ecosystem, the later-incoming culture in the early thirteenth century was marked by extensive migrations into and out of the area and abrupt shifts in hunting technologies. This has had long-lasting consequences for the local lake ecosystems. Large natural transformations in the ecosystems have also occurred over relatively short time periods related to changes in the polynya. Finally, we discuss the future perspectives for the North Water area given the many threats, but also opportunities.