The primary reason is usually lack of relevancy. If you are delivering great content that the subscriber asked for, then they will become and stay engaged for as long as it's relevant to them. If you have an high opt-out rate, evaluate how those people ended up on your list in the first place. Did you buy those emails or do you have an opt-in process that is obscure? If so, people may be opting out because they didn't formally ask to be subscribed in the first place. If they are true subscribers, map your content to your audience and see what messages are suffering from low engagement. It may also be time to rethink frequency. In any case, remove non-responders from your list. High opt-out rates and low engagement will negatively affect your email deliverability thereby preventing you from reaching the people who actually want to receive your email messages.