The subscriber key is a unique identifier for each subscriber in Marketing Cloud. It is used to track subscriber preferences, behaviors, and attributes across channels and business units. If the previous send used email address as a subscriber key, it would not match the subscriber key in Sales Cloud, which is usually the contact or lead ID. Therefore, the email opt out status would not be synchronized between Marketing Cloud and Sales Cloud, and the customer could receive an email through MCC even after unsubscribing from the previous send. Reference: https://help.salesforce.com/articleView?id=sf.mc_co_subscriber_key.htm&type=5