Recent approaches to make microalgae biotechnologically accessible show that a deep understanding of symbiotic interaction mechanisms between microalgae and its associated microbiome is mandatory. Often, the microbial diversity can be narrowed down to specific taxa thriving in the challenging microenvironment of microalgae. Tight associations between microalgae and bacteria have resulted in the evolution of a multifaceted network of cross‐kingdom interactions and a fine specialization of different organisms. Until now, the genetic background of this communication is still unclear. To address these challenges, we have analyzed the metatranscriptomic data of the microalgae Scenedesmus quadricauda MZCH 10104 and its affiliated microbiome during both the exponential phase and the stationary phase; and we established a synthetic plant-bacteria system for more direct interaction analyses. The most abundant bacteria in our datasets were affiliated with Dyadobacter (Cytophagia), Porphyrobacter (Alphaproteobacteria) and Variovorax (Betaproteobacteria) have shown to be highly active within the algae culture with respect to key genes commonly involved in plant–microbe interactions and different pathways, including the degradation of biopolymers, signal transduction mechanisms, transport mechanisms and secretion systems, metabolism of cofactors, vitamins and secondary metabolites. While being one of the main producers of microalgae-stimulating substances, Dyadobacter has also shown high relevance regarding the expression of genes responsible for invasion, root colonization and biofilm formation simultaneously interacting with possible algal innate immune system. Interestingly, a high number of reads were affiliated with various secretion and transport systems, which are responsible for the secretion of bioactive molecules to the extracellular environment.