Phycospheric bacteria may be the key biological factors affecting the growth of algae. However, the studies about interaction between Isochrysis galbana and its phycospheric bacteria are limited. Here, we show that a marine heterotrophic bacterium, Alteromonas macleodii, enhanced the growth of I. galbana, and the physiological and biochemical effects of A. macleodii on I. galbana were also analyzed. Further, we explored this phenomenon via examining how the entire transcriptomes of I. galbana and A. macleodii changed when they were co-cultured. Notable increase was observed in transcripts related to photosynthesis, carbon fixation, oxidative phosphorylation, ribosomal proteins, biosynthetic enzymes, and transport processes of I. galbana in the presence of A. macleodii, suggesting the introduction of the bacterium might have induced increased production and transport of carbon compounds and other secondary metabolites. Besides, the transcriptome changed largely corresponded to reduced stress conditions for I. galbana, as inferred from the depletion of transcripts encoding DNA repair enzymes and other stress-response proteins. For A. macleodii, the biosynthesis of protein (ribosomal genes), the utilization of carbon source (galactose metabolism), and amino acid metabolism (arginine and proline metabolism) were upregulated significantly in co-culture, while the flagellar assembling was degenerated. These results suggests that transfer of fixed organic carbon, but perhaps many other types of biomolecules, between the autotroph and the heterotroph is happened in I. galbana-A. macleodii co-culture. The present work provides novel insights into the transcriptional consequences of mutualism between I. galbana and its heterotrophic bacterial partner, and mutually beneficial associations existing in I. galbana-A. macleodii might be explored to improve productivity and sustainability of aquaculture algal rearing systems.