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Hydro-morphological threats impact the natural physical characteristics of river ecosystems, such as flow regimes, sediment transport, and channel morphology. These negative effects can occur at multiple scales, ranging from local microhabitats to geographic regions. Understanding these interactions can be useful for an integrated conservation approach and is needed for effective freshwater management. The aim of the study was to elucidate the combined effects of hydro-morphological threats on macroinvertebrates at three spatial scales: macroscale, including whole catchments, mesoscale (hydro-morphological changes in individual river sections) and the microscale, describing the microhabitat conditions of European rivers. The diversity and trophic structure of 1120 local macroinvertebrate communities in 28 catchments of various hydro-morphological disturbance levels, ranging from 0 to 2400 m asl, were analyzed. The response of macroinvertebrates to the main disturbance gradient differed between mountain and lowland communities. Random forest analysis indicated that the most important predictor of the ecological, diversity, and trophic indices was described by flow rate reduction. Generalized additive mixed models showed that decreased flow combined with river incision explained most of the variation in macroinvertebrate indices. Our results emphasize that based on multi-spatial scale analysis, hydro-morphological threats are very important factors in invertebrates biodiversity loss. Thus, to implement effective river management, we should pay more attention to the combined effects of geomorphological threats. • Hydro-morphological disturbances lead to the loss of invertebrate biodiversity. • The effects of hydro-morphological pressure were studied at various spatial scales. • Incision and flow reduction described most of the river macroinvertebrates variation. • The most favourable microhabitats for macrofauna are shallow and redeposited sites. • Efficient river management should focus on the combined effects of multiscale threats. [ABSTRACT FROM AUTHOR]